Lund-Johansen P, Omvik P, Haugland H
Br J Clin Pharmacol. 1986;21 Suppl 1(Suppl 1):45S-54S. doi: 10.1111/j.1365-2125.1986.tb02853.x.
The acute and chronic haemodynamic effects of doxazosin were studied in 14 patients (10 males, four females) with essential hypertension, at rest supine and sitting and during 100 W bicycling exercise. Blood pressure (BP) was recorded intra-arterially in the brachial artery, cardiac output (CO) was measured by Cardiogreen and heart rate (HR) by ECG. One hour after injection of doxazosin 0.5-1.0 mg i.v., mean arterial pressure (MAP) was reduced by 8% at rest supine, 12% at rest sitting and 10% at 100 W (all changes statistically significant), associated with a reduction in total peripheral resistance index (TPRI) of 5% at rest supine, 9% at rest sitting (P less than 0.01) and 14% at 100 W (P less than 0.001). HR was slightly increased (5%, NS) and cardiac index (CI) was unchanged during rest and slightly increased during exercise (4%, P less than 0.05). Patients were then given doxazosin capsules (2-16 mg once daily), aiming at a casual BP of less than or equal to 140/90 mmHg without side-effects. Central haemodynamics were restudied after 1 year. After 1 year of doxazosin treatment, MAP was reduced by 13% at rest supine, 16% at rest sitting and 17% at 100 W (all P-values less than 0.001). TPRI was reduced by 19% at rest supine, 20% at rest sitting and 18% at 100 W (all changes statistically significant). CI was increased by 8% at rest supine (P less than 0.05) but was unchanged sitting and at 100 W. It is concluded that doxazosin lowers BP through a reduction in TPRI acutely as well as chronically, without reductions in CO. BP control was maintained over 1 year without side-effects. Thus, doxazosin normalizes central haemodynamics in patients with mild to moderate essential hypertension, both at rest and during exercise.
对14例原发性高血压患者(10例男性,4例女性)进行了多沙唑嗪的急性和慢性血流动力学效应研究,研究在静息仰卧位、静息坐位以及100瓦自行车运动期间进行。通过肱动脉内动脉穿刺记录血压(BP),采用心绿(Cardiogreen)测量心输出量(CO),通过心电图测量心率(HR)。静脉注射0.5 - 1.0毫克多沙唑嗪1小时后,静息仰卧位时平均动脉压(MAP)降低8%,静息坐位时降低12%,100瓦运动时降低10%(所有变化均具有统计学意义),同时静息仰卧位时总外周阻力指数(TPRI)降低5%,静息坐位时降低9%(P < 0.01),100瓦运动时降低14%(P < 0.001)。静息时心率(HR)略有增加(5%,无统计学意义)且心指数(CI)无变化,运动期间心指数略有增加(4%,P < 0.05)。随后给予患者多沙唑嗪胶囊(每日一次,2 - 16毫克),目标是使偶测血压小于或等于140/90 mmHg且无副作用。1年后再次研究中心血流动力学。经过1年的多沙唑嗪治疗,静息仰卧位时MAP降低13%,静息坐位时降低16%,100瓦运动时降低17%(所有P值均小于0.001)。静息仰卧位时TPRI降低19%,静息坐位时降低20%,100瓦运动时降低18%(所有变化均具有统计学意义)。静息仰卧位时CI增加8%(P < 0.05),但静息坐位和100瓦运动时无变化。结论是多沙唑嗪通过急性和慢性降低TPRI来降低血压,而不降低CO。血压控制在1年以上且无副作用。因此,多沙唑嗪使轻度至中度原发性高血压患者在静息和运动时的中心血流动力学恢复正常。